Methods and Applications of Statistics in Clinical Trials, Volume 2: Planning, Analysis, and Inferential Methods

Chapter 48

Stability Study Designs

Tsae-Yun Daphne Lin and Chi Wan Chen

48.1 Introduction

The stability of a drug substance or drug product is the capacity of the drug substance or drug product to remain within the established specifications to ensure its identity, strength, quality, and purity during a specified period of time. The U.S. Food and Drug Administration (FDA) requires that the shelf life (also referred to as expiration dating period) must be indicated on the immediate container label for every human drug and biologic on the market.

A good stability study design is the key to a successful stability program. From statistical perspectives, several elements need to be considered in planning a stability study design. First, the stability study should be well designed so the shelf life of the drug product can be estimated with a high degree of accuracy and precision. Second, the stability design should be chosen so that it can reduce bias and identify and control any expected or unexpected source of variations. Third, the statistical method used for analyzing the data collected should reflect the nature of the design and provide a valid statistical inference for the established shelf life.

In many cases, the drug product may have several different strengths packaged in different container sizes because of medical needs. To test every batch under all factor combinations on a real-time, long-term testing schedule can be expensive and time consuming. As an alternative, a reduced ...